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The specific interactions between dendritic cells and Porphyromonas gingivalis

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dc.contributor.advisor Cutler, Christopher W. en_US
dc.contributor.author Zeituni, Amir Emanuel en_US
dc.contributor.other Department of Molecular Genetics and Microbiology en_US
dc.date.accessioned 2012-05-15T18:07:52Z
dc.date.accessioned 2015-04-24T14:53:23Z
dc.date.available 2012-05-15T18:07:52Z
dc.date.available 2015-04-24T14:53:23Z
dc.date.issued 2010-12-01
dc.identifier Zeituni_grad.sunysb_0771E_10289.pdf en_US
dc.identifier.uri http://hdl.handle.net/1951/55692 en_US
dc.identifier.uri http://hdl.handle.net/11401/72726 en_US
dc.description.abstract The broad objective of this dissertation is to elucidate the specific interactions between Porphyromonas gingivalis (P. gingivalis) and dendritic cells (DCs). P. gingivalis is a black pigmented, anaerobic, Gram-negative bacterium that is associated with most cases of chronic periodontitis. P. gingivalis expresses a myriad of virulence factors, most notably, fimbrial adhesins that enable it to bind to and invade host epithelial cells, endothelial cells, macrophages and DCs. While much is known about the 41 kDa major fimbria adhesins of P. gingivalis, the minor fimbriae have received little attention. The results presented here suggest that the minor fimbriae may serve as an immunosuppressive factor, by targeting the C-type lectin receptor DC-SIGN. DC-SIGN (CD209) is involved in uptake of certain pathogens by DC, in the formation of DC-T cell conjugates, and is increasingly expressed in chronic periodontitis (CP) lesions. Targeting DC-SIGN for entry into DCs has proved an effective immuno-evasive strategy for certain pathogens. DC-SIGN ligation down-modulates maturation of DCs, dampens DC secretion of pro-inflammatory and Th1-cytokines necessary for induction of protective immunity and, possibly, compromises intracellular killing mechanisms. The aim for this research was to investigate the role of the minor fimbriae of P. gingivalis in invasion of DC's and in activation of immunosuppressive innate signaling pathways. I determined that the minor fimbriae targets DC-SIGN on DCs. Furthermore, I discovered that the minor fimbriae are glycosylated with DC-SIGN targeting sugars (fucose, mannose, galactose, and N-acetylglucosamine). Detection of glycosylation was determined using endoglycosidases and then confirmed via gas chromatography-mass spectrometry (GC-MS). Finally, it was determined that minor fimbriae targeting of DC-SIGN has an immunosuppressive effect on DCs as well as on T cells co-cultured with pulsed DCs. en_US
dc.description.sponsorship This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. en_US
dc.format Monograph en_US
dc.format.medium Electronic Resource en_US
dc.language.iso en_US en_US
dc.publisher The Graduate School, Stony Brook University: Stony Brook, NY. en_US
dc.subject.lcsh Microbiology -- Immunology -- Biology en_US
dc.subject.other DC-SIGN, Dendritic Cells, Glycosylation, Immuno-modulation, Innate Immunity, Porphyromonas gingivalis en_US
dc.title The specific interactions between dendritic cells and Porphyromonas gingivalis en_US
dc.type Dissertation en_US
dc.mimetype Application/PDF en_US
dc.contributor.committeemember David G. Thanassi en_US
dc.contributor.committeemember Michael Hayman en_US
dc.contributor.committeemember Adrianus W.M. Van der Velden en_US
dc.contributor.committeemember Caroline A. Genco. en_US

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